Side-chain ionization states in a potassium channel

KcsA is a bacterial K+ channel that is gated by pH. Continuum dielectric ca lculations on the crystal structure of the channel protein embedded in a lo w dielectric slab suggest that side chains E71 and D80 of each subunit, whi ch lie adjacent to the selectivity filter region of the channel, form a pro ton-sharing pair in which E71 is neutral (protonated) and D80 is negatively charged at pH 7. When K+ ions are introduced into the system at their crys tallographic positions the pattern of proton:sharing is altered. The larges t perturbation is for a K+ ion at site S3, i.e., interacting with the carbo nyls of T75 and V76. The presence of multiple K+ ions in the filter increas es the probability of E71 being ionized and of D80 remaining neutral (i.e., protonated). The ionization states of the protein side chains influence th e potential energy profile experienced by a K+ ion as it is translated alon g the pore axis. In particular, the ionization state of the E71-D80 proton- sharing pair modulates the shape of the potential profile in the vicinity o f the selectivity filter. Such reciprocal effects of ion occupancy on side- chain ionization states, and of side-chain ionization states on ion potenti al energy profiles will complicate molecular dynamics simulations and relat ed studies designed to calculate ion permeation energetics.